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Three Part Question

In [children with strawberry naevi] when does [conservative management] result in [no further growth or resolution]?

Clinical Scenario

A 3-month-old child is seen in clinic because of a rapidly enlarging birthmark on his back. On examination it is seen to be a strawberry naevus measuring 45×25 mm. The parents want to know how much further it will enlarge and when it is likely to settle. A straw poll of staff at grand round reveals that it is reckoned that maximum size should be achieved by 13 months (median) and resolution should have occurred in half the cases at 5 years (median).

Search Strategy

Medline (1950–present) and Embase (1980–present) were searched

No relevant articles were found in BestBETs or Cochrane libraries.
strawberry naevus’, ‘haemangioma’ and ‘capillary naevus’, with each of ‘growth’, ‘regression’, ‘involution’, ‘prognosis’ and ‘complications’, with all results limited to children (15 searches in total). Overall, 130 abstracts were reviewed of which four seemed relevant. A hand search of the citations in these review articles revealed two further original studies.

Search Outcome

3 papers

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chang et al, 2008,	1096 patients with ≥1 lesion	Prospective observational study over 18 months, categorisation	Size and growth rate	Peak growth rate in first 3 months, minimal at ≥10 months	Segmental lesions grow larger and for longer than localised lesions
Lister et al, 1938	93 lesions in 77 patients	Prospective observational study over 7 years	Size and resolution - maximum size	Size: 19% still growing at 6 months, none still growing at 1 year	Observed and categorised subgroups similarly to new papers Editor note-To save space, only the details of every fourth patient recruited are given as a representative sample. Percentages have been calculated from this table
			Size and resolution - complete involution	Resolution: 52% at 3 years 74% at 4 years 93% at 5 years
Chiller et al. 2002	472 lesions in 327 patients	Retrospective case note review	Prognostic demographics and lesion subtype	84% resolving spontaneously at mean follow-up age of 16.1 months	Less likely to resolve if Hispanic, segmental lesion or mucosal involvement

Comment(s)

Our main interest was localised skin lesions commonly known as ‘strawberry naevi’. These go by various different names in the literature, hence the complicated search strategy. The papers of Chang and Chiller identify marked differences in natural history between isolated ‘strawberry naevi’ and larger ‘segmental’ lesions, which are not considered here. From the detailed descriptions of each lesion in Lister's paper, however, it is easy to determine the subtype in each case.

Chang and Lister identify representative samples of patients at a common, early stage and follow them up for an appropriate time. Size is an objective measurement and segmental lesions are dealt with separately. Lister measures and documents each individual lesion at predetermined times. In contrast, the follow-up of Chang and Chiller is based on clinical need. Where necessary growth was estimated assuming linear growth between irregular clinic visits, which would tend to prolong the growth phase. Because these visits were carried out in a tertiary dermatology unit, there may be referral bias. The timescales reported in all three original studies are similar and would appear to be a valid representation. None of the original papers mentions patients lost to follow-up.

Complications are most likely in larger haemangiomas and segmental subtypes. A recent study of 1058 patients found that the most common complication is ulceration (23.2%) and the most common location for a problematic lesion is the perineum. Rarer complications depended on lesion location and included visual compromise (6.9%), airway obstruction (1.8%), auditory canal obstruction (1.1%) and cardiac compromise (0.4%)(Haggstrom). In these situations early specialist review is called for as current treatments are more likely to reduce complications by limiting lesion growth than speeding resolution.

The prognostic advice dispensed by our group has been overly pessimistic but similar to that in two recent review articles( McLaughlin, Smolinski)which quote resolution of 50% at 5 years, 70% at 7 years and 90% at 9 years. This advice is not supported by the original studies reviewed here, which suggest peak growth within the first 6 months and resolution within the first few years.

Clinical Bottom Line

Strawberry naevi grow most rapidly in the first few months and most growth is finished by 1 year of age. (Grade B)

There is much variation in the time to resolution, but it is likely to be complete by the time the child starts primary school. (Grade B)

References

1. Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008;122:360–7.
2. McLaughlin MR, O'Connor NR, Ham P. Newborn skin: Part II. Birthmarks. Am Fam Phys 2008;77:56–60.
3. Smolinski KN, Yan AC. Hemangiomas of infancy: clinical and biological characteristics. Clin Pediatr 2005;44:747–66.
4. Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature. Pediatr Dermatol 2008;25:168–73.
5. Lister WA. The natural history of strawberry naevi. Lancet 1938;1:1429–34.
6. Chiller KG, Passaro D, Frieden IJ. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol 2002;138:1567–76.
7. Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment. Pediatrics 2006;118:882–7.